Outcomes of safety and effectiveness in a multicenter randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy
Seetha Shankaran, Athina Pappas, Abbott R Laptook, Scott A McDonald, Richard A Ehrenkranz, Jon E Tyson, Michelle Walsh, Ronald N Goldberg, Rosemary D Higgins, Abhik Das, NICHD Neonatal Research Network, William Oh, Avroy A Fanaroff, Ronald N Goldberg, Barbara J Stoll, James A Lemons, David K Stevenson, Waldemar A Carlo, Edward F Donovan, Neil N Finer, Shahnaz Duara, Dale L Phelps, Abbot R Laptook, Jon E Tyson, T Michael O'Shea, Seetha Shankaran, Richard A Ehrenkranz, Alan Jobe, Avroy A Fanaroff, Michele C Walsh, Nancy Newman, DeeAnne Wilson-Costello, Bonnie Siner, William Oh, Angelita Hensman, Betty Vohr, Lucy Noel, C Michael Cotten, Kathy Auten, Ricki Goldstein, Melody Lohmeyer, Barbara J Stoll, Lucky Jain, Ellen Hale, James A Lemons, Diana Dawn Appel, Lucy Miller, Anna Dusick, Leslie Richard, David K Stevenson, Krisa VanMeurs, M Bethany Ball, Susan R Hintz, Waldemar A Carlo, Monica Collins, Shirley Cosby, Myriam Peralta-Carcelen, Vivien Phillips, Edward F Donovan, Cathy Grisby, Barb Alexander, Jody Shively, Holly Mincey, Jean Steichen, Teresa Gratton, Neil N Finer, David Kaegi, Chris Henderson, Wade Rich, Kathy Arnell, Yvonne E Vaucher, Martha Fuller, Shahnaz Duara, Ruth Everett, Charles R Bauer, Ronnie Guillet, Linda Reubens, Gary Myers, Diane Hust, Abbot R Laptook, Susie Madison, Gay Hensley, Nancy Miller, Roy Heyne, Sue Broyles, Jackie Hickman, Jon E Tyson, Georgia McDavid, Esther G Akpa, Claudia Y Franco, Patty A Cluff, Anna E Lis, Brenda H Morris, Pamela J Bradt, Seetha Shankaran, Rebecca Bara, Geraldine Muran, Yvette Johnson, Debbie Kennedy, Richard A Ehrenkranz, Patricia Gettner, Elaine Romano, W Kenneth Poole, Betty Hastings, Carolyn M Petrie, Rosemary D Higgins, Linda L Wright, Elizabeth McClure, Gordon Avery, Mary D'Alton, W Kenneth Poole, John C Fletcher, Christine A Gleason, Carol Redmond, Seetha Shankaran, Athina Pappas, Abbott R Laptook, Scott A McDonald, Richard A Ehrenkranz, Jon E Tyson, Michelle Walsh, Ronald N Goldberg, Rosemary D Higgins, Abhik Das, NICHD Neonatal Research Network, William Oh, Avroy A Fanaroff, Ronald N Goldberg, Barbara J Stoll, James A Lemons, David K Stevenson, Waldemar A Carlo, Edward F Donovan, Neil N Finer, Shahnaz Duara, Dale L Phelps, Abbot R Laptook, Jon E Tyson, T Michael O'Shea, Seetha Shankaran, Richard A Ehrenkranz, Alan Jobe, Avroy A Fanaroff, Michele C Walsh, Nancy Newman, DeeAnne Wilson-Costello, Bonnie Siner, William Oh, Angelita Hensman, Betty Vohr, Lucy Noel, C Michael Cotten, Kathy Auten, Ricki Goldstein, Melody Lohmeyer, Barbara J Stoll, Lucky Jain, Ellen Hale, James A Lemons, Diana Dawn Appel, Lucy Miller, Anna Dusick, Leslie Richard, David K Stevenson, Krisa VanMeurs, M Bethany Ball, Susan R Hintz, Waldemar A Carlo, Monica Collins, Shirley Cosby, Myriam Peralta-Carcelen, Vivien Phillips, Edward F Donovan, Cathy Grisby, Barb Alexander, Jody Shively, Holly Mincey, Jean Steichen, Teresa Gratton, Neil N Finer, David Kaegi, Chris Henderson, Wade Rich, Kathy Arnell, Yvonne E Vaucher, Martha Fuller, Shahnaz Duara, Ruth Everett, Charles R Bauer, Ronnie Guillet, Linda Reubens, Gary Myers, Diane Hust, Abbot R Laptook, Susie Madison, Gay Hensley, Nancy Miller, Roy Heyne, Sue Broyles, Jackie Hickman, Jon E Tyson, Georgia McDavid, Esther G Akpa, Claudia Y Franco, Patty A Cluff, Anna E Lis, Brenda H Morris, Pamela J Bradt, Seetha Shankaran, Rebecca Bara, Geraldine Muran, Yvette Johnson, Debbie Kennedy, Richard A Ehrenkranz, Patricia Gettner, Elaine Romano, W Kenneth Poole, Betty Hastings, Carolyn M Petrie, Rosemary D Higgins, Linda L Wright, Elizabeth McClure, Gordon Avery, Mary D'Alton, W Kenneth Poole, John C Fletcher, Christine A Gleason, Carol Redmond
Abstract
Background: Whole-body hypothermia reduced the frequency of death or moderate/severe disabilities in neonates with hypoxic-ischemic encephalopathy in a randomized, controlled multicenter trial.
Objective: Our goal was to evaluate outcomes of safety and effectiveness of hypothermia in infants up to 18 to 22 months of age.
Design/methods: A priori outcomes were evaluated between hypothermia (n = 102) and control (n = 106) groups.
Results: Encephalopathy attributable to causes other than hypoxia-ischemia at birth was not noted. Inotropic support (hypothermia, 59% of infants; control, 56% of infants) was similar during the 72-hour study intervention period in both groups. Need for blood transfusions (hypothermia, 24%; control, 24%), platelet transfusions (hypothermia, 20%; control, 12%), and volume expanders (hypothermia, 54%; control, 49%) was similar in the 2 groups. Among infants with persistent pulmonary hypertension (hypothermia, 25%; control, 22%), nitric-oxide use (hypothermia, 68%; control, 57%) and placement on extracorporeal membrane oxygenation (hypothermia, 4%; control, 9%) was similar between the 2 groups. Non-central nervous system organ dysfunctions occurred with similar frequency in the hypothermia (74%) and control (73%) groups. Rehospitalization occurred among 27% of the infants in the hypothermia group and 42% of infants in the control group. At 18 months, the hypothermia group had 24 deaths, 19 severe disabilities, and 2 moderate disabilities, whereas the control group had 38 deaths, 25 severe disabilities, and 1 moderate disability. Growth parameters were similar between survivors. No adverse outcomes were noted among infants receiving hypothermia with transient reduction of temperature below a target of 33.5 degrees C at initiation of cooling. There was a trend in reduction of frequency of all outcomes in the hypothermia group compared with the control group in both moderate and severe encephalopathy categories.
Conclusions: Although not powered to test these secondary outcomes, whole-body hypothermia in infants with encephalopathy was safe and was associated with a consistent trend for decreasing frequency of each of the components of disability.
Trial registration: ClinicalTrials.gov NCT00005772.
Source: PubMed